The mechanism of action of ristocetin induced aggregation of platelets in the presence of the von Willebrand factor will be studied by analyzing the effects of chemical modification of ristocetin, formalinized platelets and purified von Willebrand factor. In particular, the hypothesis suggesting the importance of electrostatic interactions will be tested by alteration of carboxyl groups by carbodiimide reactions and primary amines by fluorescamine. The nature of the platelet component(s) required for ristocetin induced aggregation will be investigated by "fixation" with reagents having different biochemical specificities and enzymatic digestion of selective surface constituents. Platelet binding studies with labelled ristocetin and von Willebrand factor before and after chemical modification, enzymatic digestion and/or reaction with monospecific antifactor VIII/von Willebrand factor antibody will yield additional information. The specificity of inhibitors of ristocetin induced platelet aggregation will be determined by their effects on platelet retention.